Discovery prompts new hope for pediatric HIV cure at UMMS

Researchers refocusing efforts to replicate the results of first functional HIV cure in an infant

By Lisa M. Larson and Bryan Goodchild

UMass Medical School Communications

March 11, 2013

Fresh off the dramatic discovery of the first functional HIV cure in an infant, UMass Medical School researchers are refocusing their studies toward replicating the results.

“We never thought this was possible,” said Katherine Luzuriaga, MD, professor of pediatrics and molecular medicine, who worked with doctors from the Johns Hopkins Children’s Center and the University of Mississippi Medical Center on the stunning case of a Mississippi baby who, given very early and aggressive antiretroviral therapy, appears to have cleared most traces of HIV.

The breakthrough, announced March 3 at the 2013 Conference on Retroviruses and Opportunistic Infections in Atlanta, received international attention as only the second well-documented case of a cure, out of the more than 70 million cumulative HIV infections. It is the first time the infection was cleared with currently available medications.

"Up to this point, we believed that all children who were treated for HIV were sentenced to a lifetime of treatment,” said Dr. Luzuriaga, a nationally known pediatric HIV specialist who has spent more than two decades studying the disease at UMMS. “This case suggests that if we can treat early enough, we may be able to reduce the size and the extent of those viral reservoirs to the point that we may someday spare children a lifetime of therapy."

The baby in this case, born to an HIV-infected mother who did not have prenatal care, received therapeutic antiretroviral treatment beginning 30 hours after birth. That therapy continued until about 18 months of age, when the child was lost to follow-up and off the drugs. Months later, the child returned to the hospital and underwent repeated standard blood tests, none of which detected HIV presence in the blood. Test for HIV-specific antibodies—the standard clinical indicator of HIV infection—also remained negative throughout.

Deborah Persaud, MD, of Johns Hopkins Children’s Center, and Luzuriaga headed a team of laboratory researchers on the case, funded by the National Institutes of Health and the American Foundation for AIDS Research (amfAR). Hannah Gay, MD, of the University of Mississippi Medical Center, treated the baby. The investigators say the prompt administration of antiviral treatment likely led to the infant’s cure by halting the formation of hard-to-treat viral reservoirs—dormant cells responsible for reigniting the infection in most HIV patients within weeks of stopping therapy.

Currently, high-risk newborns—those born to mothers with poorly controlled infections or whose mothers’ HIV status is discovered around the time of delivery—receive a combination of antivirals at prophylactic doses to prevent infection for six weeks and start therapeutic doses if and once infection is diagnosed. But this particular case, the investigators say, may change the current practice because it highlights the curative potential of very early ART.

“Complete viral eradication on a large scale is our long-term goal but, for now, remains out of reach, and our best chance may come from aggressive, timely and precisely targeted use of antiviral therapies in high-risk newborns as a way to achieve functional cure,” said Luzuriaga.

UMMS is designing and preparing to launch additional lab studies and clinical trials to test the effectiveness of early and aggressive treatment of HIV in newborns.

“UMass has a long history of working in pediatric HIV infection,” Luzuriaga said. “One of the drugs that is a mainstay for either prevention of mother-to-child transmission or treatment of women and children—which is call neviraparine—was discovered in this lab and was brought into very early clinical trials here at UMass.”

In 1995, UMMS started some of the first early treatment trials of children with HIV.

“The oldest of those children are now approaching their 18th birthdays,” she said. “I think we have been able to make a major impact on pediatric HIV infection. We have benefited from the very strong research environment here, including the Center for AIDS Research and, more recently, the Center for Clinical and Translational Science.”